The elucidation of the molecular basis for sweet and bitter tastes is the long-term objective for this program. Peptide derivatives with constrained geometries will be synthesized including selected series of compounds such as the dipeptides: L-aspartyl-(E)-dehydrophenylalanine methyl ester and L-aspartyl-2-Alpha-aminoindan- and 2-Alpha-aminotetralin carboxylic acid methyl esters and substituted L-aspartyl-Alpha-aminocycloalkane carboxylic acid methyl esters. Since we have established that the tripeptide, L-aspartyl-D-alanyl-Alpha-aminoisobutyric acid methyl ester is sweet, we will prepare the series of compounds, L-aspartyl-D-alanyl-Alpha-aminocycloalkane carboxylic acid methyl esters. Lastly, we desire to synthesize the cyclic tetrapeptide, L-aspartyl-cyclo-(D-lysyl-Alpha-aminoisobutyryl-Beta-alanyl) which we believe will be sweet. Our program also includes a novel in vitro approach to assess taste properties. Antibodies will be raised to the sweet protein, monellin. We will determine the cross reactivity of numerous peptide tastants toward these antibodies and relate the immunoreactivities to their taste characteristics. By appropriate NMR studies and computer simulations, a general model for structure-taste relationships will be developed. This model will enable us to design novel, metabolically safe, noncaloric and noncariogenic sweeteners. Clearly the preparation of such molecules will be a substantial contribution to public health.